Upregulated MiR-9-5p Protects Against Inflammatory Response in Rats with Deep Vein Thrombosis via Inhibition of NF-κB p50
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Recently, microRNAs (miRNAs) have been demonstrated to play important roles in the cardiovascular system, including heart, blood vessels, plasma, and vascular diseases. Deep vein thrombosis (DVT) refers to the formation of blood clot in the deep veins of the human body and is a common peripheral vascular disease. Herein, we explored the mechanism of miR-9-5p in DVT through nuclear factor-κB (NF-κB). The expression of miR-9-5p in DVT rats was measured through the establishment of DVT rat models, followed by the alteration of miR-9-5p and NF-κB p50 in rats through the injection of constructed lentiviral vectors so as to explore the role of miR-9-5p and NF-κB p50 expression in rats. Next, the expression of NF-κB p50 and levels of inflammation-related factors plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-8 (IL-8) were measured after the injection with lentiviral vectors, followed by the assessment of platelet aggregation and TXB2 content. MiR-9-5p was found to be downregulated in DVT rats. Through dual luciferase reporter gene assay, NF-κB p50 was verified as the target gene of miR-9-5p and miR-9-5p could negatively regulate NF-κB p50. MiR-9-5p over-expression decreased the levels of PAI-1, TNF-α, IL-6, and IL-8 and platelet aggregation as well as TXB2 content, thus inhibiting thrombosis. Meanwhile, over-expressed NF-κB p50 could reverse the anti-inflammatory or anti-thrombotic effect of miR-9-5p. In summary, miR-9-5p over-expression can suppress the NF-κB signaling pathway through p50 downregulation, thus alleviating inflammation and thrombosis in DVT rats. MiR-9-5p could serve as a potential therapeutic target for DVT.
KEY WORDSdeep vein thrombosis microRNA-9-5p inhibition transcription factor nuclear factor-κB p50 inflammatory response thrombosis
We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.
This study was supported by General Program of National Natural Science Foundation (No. 81871187), Regional Projects of National Natural Science Foundation (No. 81460239), and Natural Science Foundation Project of Ningxia Hui Autonomous Region (No. NZ17195).
Compliance with Ethical Standards
All animal experiments were carried out in accordance with the principles and procedures of the National Institute of Animal Health Care Guidelines and approved by the Animal Ethics Committee of Qingdao Municipal Hospital.
Conflict of Interest
The authors declare that they have no conflict of interest.
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